EP0672651A1 - Procédé pour la préparation de 4-fluoroalcoxycinnamonitriles - Google Patents

Procédé pour la préparation de 4-fluoroalcoxycinnamonitriles Download PDF

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Publication number
EP0672651A1
EP0672651A1 EP95102766A EP95102766A EP0672651A1 EP 0672651 A1 EP0672651 A1 EP 0672651A1 EP 95102766 A EP95102766 A EP 95102766A EP 95102766 A EP95102766 A EP 95102766A EP 0672651 A1 EP0672651 A1 EP 0672651A1
Authority
EP
European Patent Office
Prior art keywords
solvent
reaction
process according
base
fluorobenzaldehyde
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP95102766A
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German (de)
English (en)
Other versions
EP0672651B1 (fr
Inventor
Matthias Dr. Beller
Klaus Dr. Colour Chemical Ltd. Forstinger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Clariant Produkte Deutschland GmbH
Original Assignee
Hoechst AG
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Publication date
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Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/36—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/37—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by etherified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
    • C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
    • C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
    • C07C47/575—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing ether groups, groups, groups, or groups

Definitions

  • the present invention relates to a new process for the preparation of 4-fluoroalkoxycinnamonitriles.
  • 4-fluoroalkoxycinnamonitriles are of technical importance as pharmaceutical intermediates. They are of particular importance as starting material for antifungal agents (ICI-D0870, Drugs of the Future, 18 (5), 424-427).
  • 4- (2,2,3,3-tetrafluoropropoxy) benzonitrile is converted to the corresponding benzaldehyde in the presence of metal hydrides such as diisobutylaluminum hydride (JPS Sho 61-72767).
  • metal hydrides such as diisobutylaluminum hydride (JPS Sho 61-72767).
  • 4- (2,2,3,3-tetrafluoropropoxy) benzaldehyde reacts with diethyl ethoxycarbonyl-methanephosphonate to give ethyl 4- (2,2,3,3-tetrafluoropropoxy) cinnamate, which is hydrolyzed to free cinnamic acid in the fourth stage.
  • the fifth reaction step consists in the formation of the cinnamic acid chloride, which in the sixth reaction stage reacts with aqueous ammonia to give 4- (2,2,3,3-tetrafluoropropoxy) cinnamic acid amide.
  • the cinnamic acid amide mentioned is converted to the desired product in the presence of thionyl chloride or phosphorus pentachloride.
  • EP 174 769 describes the synthesis of the analog 4-trifluoromethoxycinnamonitrile starting from 4-trifluoromethoxyaniline, which is successively diazotized, iodinated and then lithiated stoichiometrically. Reaction of the sensitive aryllithium reagent with dimethylformamide gives 4-trifluoromethoxybenzaldehyde, which provides the desired 4-trifluoromethoxycinnamonitrile with 1-cyanomethylphosphonic acid diethyl ester.
  • EP 174 769 has similar disadvantages as the method described in EP 0 472 392.
  • the large number of stages and the associated low overall yield and the problems with the use of stoichiometric amounts of metal organics and toxic cyanomethylphosphonic acid esters make the process unsuitable for industrial implementation.
  • the process is also very suitable for the preparation of partially fluorinated 4-fluoroalkoxycinnamonitriles of the formula (I), in which m ⁇ 2n + 1.
  • the process according to the invention is carried out as follows: 4-fluorobenzaldehyde is reacted together with the fluoroalkanol in the presence of 0.5 to 3, in particular 0.6 to 1.25, equivalents of base at temperatures between 10 ° C. and 180 ° C., in particular 60 to 155 ° C., to give 4-fluoroalkoxybenzaldehyde.
  • Suitable bases are, for example, alkali carbonates, in particular potassium carbonate, sodium carbonate or mixtures of potassium carbonate and sodium carbonate.
  • the reaction can be carried out both in the presence of dipolar aprotic solvents such as N, N-dimethylacetamide, sulfolane and N, N-dimethylformamide and also without solvents.
  • fluoroalkanol which ultimately acts as a solvent.
  • the process according to the invention can be carried out both with partial conversion and preferably with largely complete conversion based on one of the two starting materials (4-fluorobenzaldehyde or fluoroalkanol), preferably 4-fluorobenzaldehyde.
  • the valuable components are recovered by distillation.
  • the starting material used in excess is also recovered by distillation.
  • the yields of 4-fluoroalkoxybenzaldehyde according to the above method are 60% to 95%.
  • the 4-fluoroalkoxybenzaldehyde obtained is according to the invention with 0.3 to 4 equivalents, preferably with 0.6 to 2.0 equivalents, preferably with 0.8 to 1.2 equivalents of cyanoacetic acid or alkyl cyanoacetates at temperatures from 50 to 250 ° C., preferably 80 up to 180 ° C in the presence of a base or a basic catalyst to 4-fluoroalkoxycinnamonitrile.
  • alkyl cyanoacetate methyl cyanoacetate, ethyl cyanoacetate and propyl cyanoacetate have proven to be favorable.
  • amines such as pyridine, piperidine, morpholine, tri-butylamine, triethylamine, tripropylamine, benzylamine, aniline, dialkylaniline have proven themselves as base and optionally also as solvent.
  • the reaction according to the invention with cyanoacetic acid derivatives can be carried out in the absence of solvents. However, it can be advantageous to work in the presence of solvents.
  • Aromatics such as benzene, toluene, xylenes, dipolar aprotic solvents such as dimethylformamide, dimethylacetamide, dimethyl sulfoxide, sulfolane, alcohols such as ethanol, propanol, butanol, glyme or ethers such as diglyme can be used as solvents.
  • the amount of solvent is 5 to 90% by weight, based on the 4-fluoroalkoxybenzaldehyde used.
  • the reaction can be carried out continuously or batchwise. Under certain circumstances, it is advantageous to meter in or to add cyanoacetic acid or alkyl cyanoacetate during the reaction.
  • the reaction mixture is cooled and the product is isolated.
  • the crude product can be purified by distillation or recrystallization.
  • the resulting products are usually in the form of a mixture of cis and trans isomers with respect to the double bond.
  • the base or the base catalyst can in principle be used homogeneously or heterogeneously.
  • the new two-stage process is clearly superior to the process described in EP 0 472 392 and EP 174 769, since the product is obtained in only two reaction steps compared to seven or 5 steps.
  • the overall yield of 4-fluoroalkoxycinnamonitrile by the process according to the invention is approximately 80% and could therefore be significantly improved compared to EP 0 472 392.
  • the method according to the invention is clearly superior economically and ecologically to the previously known old method.
  • the filtrate and washing toluene are collected separately. After distilling off 63.9 g of 2,2,3,3-tetrafluoropropanol from the filtrate, the distillation residue is combined with the washing toluene. After the toluene has been distilled off at normal pressure, the residue is fractionated in vacuo at 3 mbar and up to 135 ° C. bottom temperature and 109 ° C. to 110 ° C. top temperature. The main course obtained is 188.7 g of 4- (2,2,3,3-tetrafluoropropoxy) benzaldehyde with a purity (GC) of 98% to 99%. Yield: 79.9%
  • the salt is washed with 50 ml of toluene.
  • the washing toluene is combined with the filtrate.
  • the residue is fractionated in vacuo at 3 mbar and up to 135 ° C. bottom temperature and 109 ° C. to 110 ° C. top temperature.
  • 15 g of 4-fluorobenzaldehyde and 185.4 g of 4- (2,2,3,3-tetrafluoropropoxy) benzaldehyde with a purity (GC) of 98% to 99% are obtained as the main run. Yield: 88.7%

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP95102766A 1994-03-10 1995-02-27 Procédé pour la préparation de 4-fluoroalcoxycinnamonitriles Expired - Lifetime EP0672651B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE4408083 1994-03-10
DE4408083A DE4408083C1 (de) 1994-03-10 1994-03-10 Verfahren zur Herstellung von 4-Fluoralkoxyzimtsäurenitrilen

Publications (2)

Publication Number Publication Date
EP0672651A1 true EP0672651A1 (fr) 1995-09-20
EP0672651B1 EP0672651B1 (fr) 1998-12-09

Family

ID=6512411

Family Applications (1)

Application Number Title Priority Date Filing Date
EP95102766A Expired - Lifetime EP0672651B1 (fr) 1994-03-10 1995-02-27 Procédé pour la préparation de 4-fluoroalcoxycinnamonitriles

Country Status (7)

Country Link
US (1) US5569776A (fr)
EP (1) EP0672651B1 (fr)
JP (1) JPH0841005A (fr)
KR (1) KR950032093A (fr)
CA (1) CA2144271A1 (fr)
DE (2) DE4408083C1 (fr)
ES (1) ES2126167T3 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4408083C1 (de) * 1994-03-10 1995-01-26 Hoechst Ag Verfahren zur Herstellung von 4-Fluoralkoxyzimtsäurenitrilen
DE4439836C1 (de) * 1994-11-08 1996-06-05 Hoechst Ag cis-4-(2,2,3,3-Tetrafluorpropoxy)-zimtsäurenitril und trans-4-(2,2,3,3-Tetrafluorpropoxy)- zimtsäurenitril und ein Verfahren zu ihrer Herstellung
US20070299276A1 (en) * 2006-06-22 2007-12-27 Andrew Edward Feiring Preparation of fluoroalkoxystyrenes

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0174769A1 (fr) * 1984-09-05 1986-03-19 Imperial Chemical Industries Plc Composés azoliques antifongiques
DE4408083C1 (de) * 1994-03-10 1995-01-26 Hoechst Ag Verfahren zur Herstellung von 4-Fluoralkoxyzimtsäurenitrilen

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2583194A (en) * 1948-04-27 1952-01-22 Eastman Kodak Co Vitamin a derivatives and methods of preparing the same
US3636073A (en) * 1967-07-03 1972-01-18 Merck & Co Inc (4-(2-cyanovinyl)phenoxy)acetic acids
CA1118450A (fr) * 1978-03-20 1982-02-16 Willem Lenselink Nitriles a base de menthanes
DE3400689A1 (de) * 1984-01-11 1985-07-18 Chemische Werke Hüls AG, 4370 Marl Verfahren zur herstellung von cyclododecenylacetonitril und seine verwendung als riechstoff oder riechstoffkomponente
TW211006B (fr) * 1990-08-24 1993-08-11 Mochida Pharm Co Ltd

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0174769A1 (fr) * 1984-09-05 1986-03-19 Imperial Chemical Industries Plc Composés azoliques antifongiques
DE4408083C1 (de) * 1994-03-10 1995-01-26 Hoechst Ag Verfahren zur Herstellung von 4-Fluoralkoxyzimtsäurenitrilen

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
G.P. SCHIEMENZ ET AL.: "Substituenteneinflüsse bei der Reaktion aromatischer Aldehyde mit Cyanessigsäure", CHEMISCHE BERICHTE, vol. 95, WEINHEIM DE, pages 967 - 970 *
J.P. IDOUX ET AL.: "Aromatic Fluoroalkoxylation via Direct Aromatic Nucleophilic Substitution", JOURNAL OF ORGANIC CHEMISTRY, vol. 48, EASTON US, pages 3771 - 3773 *

Also Published As

Publication number Publication date
DE59504456D1 (de) 1999-01-21
ES2126167T3 (es) 1999-03-16
KR950032093A (ko) 1995-12-20
EP0672651B1 (fr) 1998-12-09
US5569776A (en) 1996-10-29
DE4408083C1 (de) 1995-01-26
JPH0841005A (ja) 1996-02-13
CA2144271A1 (fr) 1995-09-11

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